1. Field of the Invention
The invention is directed to methods and materials for the treatment of penile defects by employing an implant comprising corporal cavernosal tissue grown on a support, and in particular to methods and materials useful in the reconstruction of an erectile penis.
2. Description of the Background
The penis or phallus, is the male organ of copulation and of urinary excretion, comprising a root, body, and extremity, or glans penis. The structure of the penis consists of two parallel cylindrical bodies, the corpora cavernosa and beneath them the corpus spongiosum, through which the urethra passes. The root of the penis is attached to the descending portions of the pubic bone by the crura, the latter being the extremities of the corpora cavernosa. The urethra runs along the underside of the penis then rises to open at the expanded, cone-shaped tip, the glans penis, which fits like a cap over the end of the penis. The cavema, also called the cavernae, corporum, or cavernosorum penis referred to the caverns of corpora cavernosa of the penis or the dilatable spaces within the corpora cavernosa of the penis, which fill with blood and become distended with erection. Loose skin encloses the penis and also forms the retractable foreskin or prepuce. Corporal, corporeal and corporic are terms used to describe tissues which are derived from the corpora cavernosa or which can be developed, differentiated, or altered by natural or artificial means into corpora cavernosa tissue.
A variety of congenital and acquired genitourinary tract abnormalities require surgical reconstruction and/or augmentation of the phallus. Surgeons approaching such diverse conditions as ambiguous genitalia, extrophy-epispadias complex, micropenis, aphallia, severe chordee, clubbed penis, concealed penis, double penis, webbed penis (penis palmatus), penis plastica, impotence, female to male genital reassignment, ventral hypospadias, and retracted phallus (in patients with spinal cord injury and traumatically or surgically acquired penile defects), encounter common difficulties presented by the lack of sufficient normal corporal tissue for satisfactory, functional phalloplasty (Woodhouse, C. R. J.: J. Urol., 152: 645, 1994; Atala, A et al. J. Urol., 150: 745, 1993).
Current operative modalities designed for penile reconstruction and lengthening commonly rely upon techniques developed for treatment of the epispadiac associated short phallus. Although these techniques, such as lysis of the suspensory ligament of the penis or corporal detachment from the ischiopubic rami, which were designed to free the corpora from their ligamentous attachments, have resulted in increases in the visible length of the penis, they are limited by their inherent dependence upon the presence of sufficient native corporal tissue. Many of these patients, even if potent, are dissatisfied because of limitations in penile length.
Operations designed for total or near total phalloplasty using free flap techniques may produce aesthetically acceptable results, but have been disappointing in obtaining sufficient rigidity to allow for sexual penetration. Autograft tissues, alone or in concert with synthetic penile prostheses, have been unable to satisfactorily replace the highly specialized erectile function of the penis. In addition, autologous and synthetic implants alike have resulted in numerous complications including erosion, extrusion, resorption, curving and dislodgment. It is clear that current procedures are limited because of the lack of a good substitute for normal, functional erectile tissue (Horton, C. E. and Dean, J. A.: World J. Surg., 14: 757,1990; Hage, J. J., and De Graaf, F. H.: Microsur., 14: 592, 1993).
Surgical techniques have also been inadequate in addressing the symptoms of impotence. There are many causes of impotence. Organic impotence is the loss of the ability to obtain or maintain a functional erection due to the interruption of certain physiologic processes. Causes of organic impotence include trauma such as spinal cord injury or pelvic fracture; postoperative complications such as prostatectomy, cystectomy, external sphincterotomy and abdominal perineal resection; vascular disease such as arteriosclerosis or priapism; neurologic disease such as peripheral neuropathy and multiple sclerosis; endocrinologic and metabolic disease such as diabetes, hypogonadism and renal failure; and medication such as estrogen, parasympatholytic, morphine, and heroin. The complex reflexes entailed in the mechanism of erection are also affected by physiological factors.
Phallic construction was initially attempted in the late 1930""s using autogenous tissue (See e.g., Goodwin, W. E. et al., Phalloplasty. J. Urol., 68: 903, 1952). Rib cartilage has been used as a stiffener in patients with traumatic penile loss. This method involves multiple stage surgery which does not have a cosmetically satisfactory result (Frumpkin, A. P.: Am. Rev. Sov. Med., 2: 14, 1944). Silicone prostheses have become popularized in the 1970s (Bretan, P. N. Jr.: In: Genitourinary Prostheses. Montague, D. K. (ed), Philadelphia, W. B. Saunders Co., 1989; Small, M. P. et al., Urology, 5: 479, 1975) Although silicone penile prostheses are an accepted treatment modality for adults, complications such as erosion and infection remain a problem (Nukui, F. et al., Int. J. Urol., 4: 52, 1997; Kardar, A. et al., Scan. J. Urol. and Nephrol., 29: 355, 1995). Other problems reported with synthetic prostheses include extrusion through the urethra or sink of the dorsal penile shaft; lymphatic edema; irritation of the glans at the corona; slippage of the glans over the prosthesis; infection of the corpora cavernosa; crural perforation; midshaft septal perforation; and penile pain (Small, M. P. et al., Urology, 5: 479, 1975).
Although silicone penile prostheses are an accepted treatment modality for adults requiring penile reconstruction, its use has not been generally applied to the pediatric population, mainly due to the long term problems associated with these artificial devices. Thus, there is a need for biocompatible and elastic penile implants that could be used in children who require genital reconstruction.
The disadvantages of current methods have placed serious limitations on phallic reconstruction. For example, genotypic male infants born with severe pseudohermaphroditism and/or microphallus may be subjugated to gender reassignment because of the physician""s inability to provide a sufficiently sized, functional neophallus. Similarly, lacking the option of receiving functional erectile tissue by transplant, the impotent patient with severe corporal fibrosis and myopathy, unresponsive to vasoactive therapeutic agents or vascular bypasses, is left with the ultimate choice of penile prosthesis placement, and is denied the future prospect of regaining normal penile erectile function.
The present invention overcomes the problems and disadvantages associated with current strategies and designs in tissue and organ reconstruction for reforming structural support members.
One embodiment of the invention is directed to an implantable prosthetic structure for use in treating a patient having an anatomical defect or erectile defect. The structural member is made from a polymeric matrix shaped in the form of a desired structural support member with dissociated corporal cavernosal cells deposited on and in the matrix such that when the matrix is implanted, a corporal cavernosal structure member is formed. The prosthetic corporal cavernosal structure has controlled biomechanical properties to provide the required structural support with erectile function in the area of the defect.
A further embodiment of the invention is directed to a method for reconstructing the penis of a patient who needs such treatment. A biocompatible synthetic or natural polymeric matrix shaped to form a structural member and adopted to fit within the corpora cavernosa or to replace the corpora cavernosa is provided. Corporal cavernosal cells are deposited on and in the polymeric matrix to form a matrix/cell construct. The matrix/cell construct is implanted into the corpora cavernosa of the patient, so that a prosthetic corporal cavernosal structure is formed in vivo with controlled biomechanical properties, thus providing the reconstructed penis with sufficient stiffness and bending strength when erect to serve as a functional organ.
While cultured cavernosum cells seeded on polymers will form corporal muscle when implanted in vivo, preferred reconstructed corporal tissue contains both endothelial and muscle cells. Therefore, this invention provides a method for developing corporal tissue in vivo by combining smooth muscle with endothelial cells (FIG. 1). Other embodiments and advantages of the invention are set forth, in part, in the description which follows and, in part, will be obvious from this description and may be learned from the practice of the invention.